This proposal has two general aims: first, to determine the nature and overall significance of the virus-immune thymus-derived lymphocyte (T cell) response in influenza and second, to use the biological characteristics of influenza viruses to define both the antigens recognized by cytotoxic T cells and the T cell receptor itself. Analysis of the pathogenesis question involves applying newly-established methods, developed for investigating cell-mediated immunity (CMI) in ectromelia and lymphocytic choriomeningitis, to influenza. Is the ultimate consequence of CMI beneficial or deleterious to the host? What roles do the different T cell subsets play in the pathogenesis of influenza pneumonia? Influenza offers unique opportunities for analyzing both T cell specificity and T cell memory in a virus system. Recurrent epidemics of influenza in man have provided a range of biologically-similar, but serologically-distinct, A strain influenza viruses. Recombinants between these viruses are readily available, and the characteristics of influenza proteins are well defined both molecularly and serologically. We intend to apply these sophisticated techniques to the problem of T cell recognition. Are the antigens recognized by immune T cells coded for by the influenza genome, or are both host and viral components involved? Does the T cell recognition structure share idiotype specificities with secreted Ig? Such information would be of great general relevance to the comprehension of T cell surveillance. Furthermore, a clear understanding of both T cell memory and specificity patterns and the role of CMI in the pathogenesis of influenza may prove invaluable for developing rational immunization procedures which would minimize the consequences of future pandemics.